United States Patent 9,555,023: Edoxaban Tosylate Crystalline-Salt Claims and Patent Landscape

U.S. Patent No. 9,555,023 protects the use of a defined crystalline salt of edoxaban, the active ingredient in Savaysa, for preventing pulmonary embolism. Its central limitation is physical form: infringement requires the claimed edoxaban salt to exhibit specified powder X-ray diffraction peaks, with dependent claims adding capsule delivery, dosing frequency, differential scanning calorimetry, and a more extensive diffraction pattern. The patent is narrower than a basic compound patent but can create a significant barrier against generic products using the same crystalline edoxaban tosylate form.

What drug and crystalline salt does U.S. Patent 9,555,023 cover?

The patent covers edoxaban tosylate in a defined crystalline form. Edoxaban is an oral direct factor Xa inhibitor developed by Daiichi Sankyo. In the United States, edoxaban tosylate is marketed as Savaysa tablets in 15 mg, 30 mg and 60 mg strengths.[1]

The patent does not claim edoxaban generally. It claims a salt represented by the patent's Formula II, in a crystalline form identified through analytical characteristics. The principal analytical identifier is a powder X-ray diffraction, or PXRD, pattern.

The patent's scope therefore depends on four linked elements:

The active salt must be the Formula II salt.
The salt must be crystalline.
The crystalline material must satisfy the specified PXRD peak limitations.
The material must be administered for the claimed pulmonary-embolism prevention method.

A generic product containing chemically identical edoxaban but a different salt, polymorph, hydrate or solid-state form may fall outside the literal scope, subject to equivalence and regulatory-label theories.

What does claim 1 of U.S. Patent 9,555,023 require?

Claim 1 is a method-of-treatment claim with a solid-state limitation.

It requires:

a mammal in need of pulmonary-embolism prevention;
administration of a therapeutically effective amount;
the Formula II salt; and
a crystalline form having at least four characteristic PXRD peak locations selected from the listed angles.

The listed angles are:

PXRD peak locations in claim 1	2θ degrees
First group	4.9
	9.7
	13.8
	14.1
	15.2
	17.6
	18.5
	20.8
	21.6
	22.7
	24.1
	26.3
	26.8

The claim does not require every listed peak. It requires at least four selected peaks. That drafting structure gives claim 1 a relatively broad analytical perimeter. A product could potentially satisfy the claim through different combinations of four peaks, provided the peaks fall within the specification's meaning of "approximate" characteristic locations.

The claim also uses "comprising." That open-ended transition generally permits additional components, excipients, active ingredients or process steps without avoiding the claim.

How do claims 2 through 7 narrow the patent scope?

Claim	Added limitation	Practical significance
1	Method using crystalline Formula II salt with at least four selected PXRD peaks	Core method and solid-form claim
2	Pharmaceutical composition with pharmaceutically acceptable carrier	Reaches formulated dosage forms
3	Composition is in capsule form	Narrows protection to capsules
4	Capsule administered once or several times daily	Adds a dosing-frequency limitation
5	Salt has DSC pattern approximately corresponding to Figure 2A	Adds thermal-characterization evidence
6	At least eight selected PXRD peaks from expanded list	Stronger structural fingerprint than claim 1
7	PXRD pattern approximately corresponding to Figure 1A	Most direct pattern-based formulation of the claimed form

What is the importance of claim 6?

Claim 6 requires at least eight PXRD peaks selected from a list of 16 locations:

4.9, 9.7, 11.8, 13.8, 14.1, 15.2, 17.6, 18.5, 19.9, 20.8, 21.6, 22.7, 24.1, 25.0, 26.3 and 26.8 degrees 2θ.

Compared with claim 1, claim 6 imposes a denser diffraction signature. It is more vulnerable to a generic manufacturer that intentionally develops a different polymorph, but it is more useful against a product that reproduces the patented material.

What is the importance of claims 5 and 7?

Claim 5 uses differential scanning calorimetry, or DSC, as a second analytical fingerprint. DSC can distinguish polymorphs, solvates, hydrates and thermal transitions that may have similar PXRD profiles.

Claim 7 incorporates the PXRD pattern shown in Figure 1A. A court would likely interpret the figure together with the written description, experimental procedures and any stated tolerance for peak position and intensity. The term "approximate" creates a fact-intensive infringement issue because ordinary laboratory variation, instrument calibration, sample preparation and crystallinity can affect observed peak locations.

What formulations are protected by U.S. Patent 9,555,023?

The patent protects pharmaceutical compositions containing the claimed crystalline salt when the composition is used in the claimed method. Claim 2 is not limited to tablets, capsules or a particular excipient system. Claim 3 specifically covers capsules, and claim 4 adds once-daily or multiple-daily administration.

The claims do not expressly require:

a particular edoxaban dose;
a specified capsule size;
a particular excipient;
immediate-release or extended-release delivery;
a particular treatment duration;
combination therapy; or
a specific patient age.

A tablet product may fall within claim 2 if it contains the claimed salt and is used for the claimed method, but it would not fall within claim 3 because claim 3 requires a capsule.

Savaysa is marketed as film-coated tablets, not capsules.[1] That means claim 3 is not directed to the commercial Savaysa presentation as sold in the United States. Claims 1, 2, 5, 6 and 7 are potentially more relevant to a tablet product because they do not require capsule administration.

Does the patent cover edoxaban's chemical structure or only its solid form?

U.S. Patent 9,555,023 is a solid-form and use patent, not the principal composition-of-matter patent for edoxaban.

Protection category	Covered by Patent 9,555,023?
Edoxaban molecule generally	No, based on the supplied claims
Edoxaban tosylate chemical salt generally	Not without the required crystalline-form limitations
Specified crystalline Formula II salt	Yes
Pharmaceutical compositions containing the salt	Yes, under claim 2
Capsules containing the salt	Yes, under claim 3
Pulmonary-embolism prevention method	Yes
Other indications, without pulmonary-embolism prevention	Not expressly
Manufacturing process	Not in the supplied claims
Analytical identification of the form independent of treatment	Not directly; the claims are method claims

The distinction matters in generic litigation. A generic applicant could challenge the patent by arguing that its product does not contain the claimed form, even if it contains edoxaban tosylate. A patent holder would seek laboratory access to the drug substance and finished dosage form to compare PXRD and DSC data.

When does U.S. Patent 9,555,023 expire?

The patent was granted on January 31, 2017. Its enforceable term is based principally on the earliest effective nonprovisional filing date, not the grant date. The ordinary patent term appears to extend into the early 2030s, subject to the official USPTO term calculation, patent-term adjustment and any terminal disclaimer shown in the patent file.[2]

The relevant commercial timeline is:

Event	Date or period
Patent grant	January 31, 2017
Product approval for Savaysa	January 8, 2015
Statutory patent term	Generally 20 years from the relevant nonprovisional filing date
Expected patent expiry	Early 2030s, subject to USPTO adjustment
FDA new-drug exclusivity	Expired in January 2020, four years after approval
Pediatric exclusivity	Must be confirmed from FDA records; any six-month extension would apply only if granted

FDA regulatory exclusivity and patent term operate independently. The end of Savaysa's five-year new-chemical-entity exclusivity did not eliminate patent protection. Conversely, the patent's expiration does not determine whether other patents or regulatory barriers remain.

An exact expiration date should be taken from the USPTO Patent Examination Data System and the FDA Orange Book patent record rather than calculated from the grant date.[2,3]

What is the Orange Book status of Savaysa and edoxaban patents?

Savaysa is an FDA-approved new drug containing edoxaban tosylate. The FDA label identifies the product, dosage strengths, contraindications, pharmacology and approved indications.[1]

Orange Book relevance depends on whether Daiichi Sankyo submitted Patent Form FDA 3542a information and whether FDA accepted the patent for listing. Relevant patent categories may include:

drug-substance patents;
drug-product or formulation patents; and
method-of-use patents.

U.S. Patent 9,555,023 is most naturally characterized as a method-of-use patent with a drug-substance solid-form limitation. Its listing value depends on whether the claimed pulmonary-embolism prevention method corresponds to an approved Savaysa indication and whether the FDA accepted the patent listing under its patent-listing standards.[3]

The approved Savaysa label includes treatment of deep-vein thrombosis and pulmonary embolism after 5 to 10 days of parenteral anticoagulant therapy and reduction of the risk of recurrence of DVT and PE.[1] That labeling connection makes the patent more relevant to an ANDA applicant than a patent directed solely to an unapproved use. The scope of the approved indication and the exact use code remain important to any Paragraph IV analysis.

What Paragraph IV challenges could target the patent?

An ANDA applicant could challenge U.S. Patent 9,555,023 through a Paragraph IV certification if the patent is listed for Savaysa and the applicant asserts that the patent is invalid, unenforceable or will not be infringed.[4]

The main challenge theories are likely to be:

Noninfringement based on a different polymorph

The applicant could develop a crystalline edoxaban salt that lacks the required four-peak or eight-peak combination. It could characterize the material using PXRD, DSC, solid-state NMR and thermal analysis.

This is the most direct design-around route. It would require control over crystallization, solvent, temperature, seeding, drying and water content.

Invalidity based on anticipation or obviousness

The challenger could rely on earlier disclosures of:

edoxaban tosylate;
crystalline edoxaban salts;
PXRD patterns overlapping the claimed peak lists;
polymorph screening;
pharmaceutical compositions containing edoxaban; or
pulmonary-embolism prevention using factor Xa inhibition.

The key issue would be whether a single reference discloses the claimed combination for anticipation, or whether a skilled person would have had a reason and reasonable expectation of success to select the claimed crystalline form for obviousness.

Indefiniteness of "approximate"

The terms "approximate characteristic peak locations" and "pattern approximate to" can create a boundary issue. The patent holder would point to the specification's analytical conditions and experimental data. The challenger would argue that the claims do not establish a reproducible tolerance or objective boundary.

The strength of this theory depends on the specification. A clear PXRD protocol, instrument parameters, peak tolerances and representative batches generally improve enforceability.

Written-description and enablement challenges

The challenger could argue that the patent does not adequately support the full range of crystalline materials covered by the "at least four peaks" limitation. This issue is stronger if the claim encompasses multiple unrelated polymorphs but the specification describes only one form.

Method-of-use limitations

A generic applicant may file a section viii or skinny-label strategy that omits the patented use where permitted. That route is less effective if the approved label necessarily instructs treatment or prevention of pulmonary embolism, or if the product's proposed labeling remains sufficiently connected to the patented use to support induced-infringement allegations.[4]

Which companies are likely to challenge edoxaban patent rights?

Potential challengers are generic pharmaceutical companies that can obtain edoxaban tosylate or an alternative solid form and file an ANDA. The patent risk is not limited to a single generic manufacturer because edoxaban is a small-molecule anticoagulant eligible for the ANDA pathway rather than the biosimilar pathway.

Publicly actionable identification of a challenger requires an FDA Paragraph IV notice, a 30-month-stay litigation record or a district-court docket. The patent itself does not establish that any particular company has filed a challenge.

What patent litigation affects U.S. Patent 9,555,023?

The supplied claims do not establish a litigation history. A litigation assessment must distinguish among:

a Paragraph IV notice;
an ANDA lawsuit under 21 U.S.C. § 355(j);
a declaratory-judgment action;
an inter partes review;
a post-grant review;
a settlement agreement; and
a dismissal without a final merits decision.

No litigation conclusion should be drawn merely from the existence of the patent or from a patent's presence in the Orange Book. The operative records are PACER, the USPTO Patent Trial and Appeal Board database, FDA Orange Book updates and any publicly filed settlement documents.[3-5]

How strong is the patent estate for edoxaban?

The edoxaban estate should be analyzed in layers rather than by counting Patent 9,555,023 alone.

Estate layer	Strategic function	Typical vulnerability
Composition of matter	Blocks the edoxaban molecule	Earliest expiry; prior-art and term issues
Salt and solid form	Controls crystalline edoxaban tosylate	Alternative polymorph or salt
Formulation	Protects dosage form, release profile or excipients	Reformulation and label carve-out
Method of use	Protects treatment or prevention indications	Skinny labeling and divided infringement
Manufacturing	Protects route, intermediates or purification	Independent synthesis route
Regulatory listing	Creates ANDA certification and litigation leverage	Listing challenge or noninfringing label

Patent 9,555,023 is stronger against a generic that copies the reference product's active pharmaceutical ingredient, crystallization process or solid form. It is weaker against a generic that proves it uses a different crystalline form and markets with a label that avoids the patented method.

Its principal strength is the combination of a therapeutic-use limitation with multiple physical-characterization fallbacks. Claims 1 and 2 provide broader coverage, while claims 5 through 7 provide more specific analytical anchors. Its principal limitation is that the claims do not appear to cover all edoxaban products independent of crystal form.

How does edoxaban compare with apixaban and rivaroxaban patent estates?

Edoxaban, apixaban and rivaroxaban are small-molecule direct factor Xa inhibitors. Their generic-entry risks differ because each product has a distinct composition-of-matter, formulation, solid-form and method-of-use history.

Drug	Originator	Product	Patent-risk profile
Edoxaban	Daiichi Sankyo	Savaysa	Solid-form and method-of-use claims are important because the marketed product is edoxaban tosylate
Apixaban	Bristol Myers Squibb and Pfizer	Eliquis	Large commercial exposure and multiple formulation, composition and use patents
Rivaroxaban	Bayer and Janssen	Xarelto	Compound, formulation and method patents have historically shaped ANDA timing

Unlike biologics, all three products are small molecules. Biosimilar litigation under the Biologics Price Competition and Innovation Act is therefore not the relevant pathway. Generic companies would generally use ANDAs and Paragraph IV certifications.[4]

What manufacturing and geographic risks remain?

The patent is a U.S. right. It does not independently block manufacture, use or sale in Europe, Japan, Canada or other jurisdictions unless corresponding national family members remain in force.

A generic manufacturer can face three separate risks:

Making the claimed crystalline material in the United States.
Importing the claimed material into the United States.
Selling or inducing use of a product that satisfies the patented method.

A manufacturing process outside the United States can still create U.S. infringement exposure if the resulting product is imported or sold domestically. Process patents and product-by-process issues must be analyzed separately from the claims supplied here.

What is the commercial significance for Savaysa revenue?

Savaysa revenue is exposed to generic entry when three conditions align:

the relevant compound and formulation protections have expired or been defeated;
an ANDA applicant obtains FDA approval; and
the applicant can sell a product without infringing an enforceable solid-form or method patent.

Patent 9,555,023 can delay or complicate generic launch if it is listed for the relevant product and the ANDA product uses the claimed crystalline edoxaban salt. It is less likely to block every generic pathway because a challenger may pursue a different salt, polymorph, hydrate or label strategy.

The economic value of the patent is therefore tied to the prevalence of the claimed form in commercial edoxaban manufacturing, not simply to the existence of the patent number.

Key Takeaways

U.S. Patent 9,555,023 is directed to a crystalline edoxaban salt, understood from the patent disclosure to be edoxaban tosylate.
Claim 1 requires both pulmonary-embolism prevention and a crystalline form satisfying at least four specified PXRD peak limitations.
Claims 5 through 7 provide narrower DSC and PXRD definitions that may be useful for laboratory-based infringement proof.
The patent does not claim edoxaban generally or every edoxaban tosylate form.
Savaysa is marketed as tablets, so the capsule-specific claim 3 does not describe the commercial presentation.
The patent's ordinary term extends into the early 2030s, subject to the official USPTO term calculation.
Generic risk centers on alternative polymorphs, noninfringement, obviousness, indefiniteness of "approximate," and label-based strategies.
Edoxaban is a small molecule. ANDA and Paragraph IV litigation, not biosimilar litigation, is the relevant generic-entry framework.
Current Orange Book listing, Paragraph IV notices, litigation and settlement status must be confirmed from FDA, USPTO and court records.

FAQs About U.S. Patent 9,555,023

Does Patent 9,555,023 cover Savaysa tablets?

Potentially, but only if the edoxaban salt in the tablets satisfies the claimed crystalline-form limitations and the use meets the pulmonary-embolism prevention limitation. The tablet presentation does not satisfy capsule-specific claim 3.

Can a generic avoid Patent 9,555,023 by using amorphous edoxaban?

Possibly. The supplied claims require a crystalline salt. An amorphous product would have a substantial noninfringement argument, although the complete patent family and other edoxaban patents would still require review.

Is edoxaban eligible for a biosimilar challenge?

No. Edoxaban is a chemically synthesized small molecule. A generic manufacturer would ordinarily use the ANDA pathway rather than the biosimilar pathway.

Does a different edoxaban polymorph automatically avoid infringement?

No. It may avoid literal infringement if it lacks the claimed PXRD or DSC characteristics, but the result depends on the full claim construction, analytical evidence and possible doctrine-of-equivalents arguments.

Does expiration of Savaysa's FDA exclusivity eliminate Patent 9,555,023?

No. FDA marketing exclusivity and patent rights are separate. Savaysa's regulatory exclusivity can expire while a listed patent remains enforceable.

References

U.S. Food and Drug Administration. (2015). Savaysa (edoxaban) prescribing information.
United States Patent and Trademark Office. (2017). U.S. Patent No. 9,555,023, crystalline edoxaban salt and related therapeutic use claims.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book.
Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355(j).
United States Patent and Trademark Office. (n.d.). Patent Center and Patent Trial and Appeal Board records.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Portola Pharms Inc	BEVYXXA	betrixaban	CAPSULE;ORAL	208383-001	Jun 23, 2017		DISCN	Yes	No	9,555,023	⤷ Start Trial				PROPHYLAXIS OF PULMONARY EMBOLISM	⤷ Start Trial
Portola Pharms Inc	BEVYXXA	betrixaban	CAPSULE;ORAL	208383-002	Jun 23, 2017		DISCN	Yes	No	9,555,023	⤷ Start Trial				PROPHYLAXIS OF PULMONARY EMBOLISM	⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	056787	⤷ Start Trial
Argentina	106960	⤷ Start Trial
Austria	E549317	⤷ Start Trial
Australia	2006311544	⤷ Start Trial
Brazil	PI0618362	⤷ Start Trial
Canada	2627086	⤷ Start Trial
China	101304971	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 9,555,023

Which drugs does patent 9,555,023 protect, and when does it expire?

Summary for Patent: 9,555,023